INTERLEUKIN-6 RECEPTOR GENE POLYMORPHISM IS ASSOCIATED WITH BOTH INCREASED INTERLEUKIN-6 BLOOD LEVEL AND BIOPROSTHETIC MITRAL VALVE CALCIFICATION

DOI: https://doi.org/None

Ponasenko A.V., Khutornaya M.V., Kutikhin A.G., Khryachkova O.N., Kondyukova N.V., Yuzhalin A.E., Rutkovskaya N.V., Barbarash O.L., Barbarash L.S.

Introduction. Valvular calcification precedes the development of valvular stenosis. Currently, there being no way to effectively prevent the valvular heart disease progression, and valve replacement remains to be the only treatment option. Aim. To investigate the genes encoding innate immune soluble molecules with the aim to find polymorphisms with functional consequences that can predict the risk of mitral valve disease and bioprosthetic mitral valve failure due to calcification. Methods. A total of 80 consecutive Russian patients who underwent mitral valve replacement surgery due to the mitral valve disease and 300 healthy age, gender, and ethnicity-matched blood donors have been recruited in the study. Genotyping has been carried out in 96-well format using the TaqMan SNP genotyping assay. The blood level of cytokines has been measured by enzyme-linked immunosorbent assay. Results. We found that C/C genotype of rs2228145 polymorphism within IL6R gene, C/T genotype of rs2229238 polymorphism within IL6R gene, and C/C genotype of rs2227306 polymorphism within IL8 gene are significantly associated with the elevated interleukin-6 and interleukin-8 blood level, respectively. Moreover, C allele of rs1800796 polymorphism within IL6 gene has been associated with increased risk for the mitral valve disease (OR=1,96, 95% CI: 1,03–3,72; р=0,046), whilst C/T genotype of rs2229238 polymorphism within IL6R gene correlated with the declined riskfor the mitral valve disease (OR=0,57, 95%CI: 0,32–1,01; р=0,047). According to the logistic regression, C/T genotype of rs2229238 polymorphism within IL6R gene has been significantly associated withthe bioprosthetic mitral valve failure due to calcification (OR=3,81, 95% CI: 1,22–11,91; р=0,021). Conclusion. We suggest that IL6R rs2229238 and IL6 rs1800796 polymorphisms may be important in the development of the mitral valve disease and bioprosthetic mitral valve calcification.
Keywords: 
valvular heart disease, mitral annular calcification, interleukins, gene polymorphisms, bioprosthetic heart valve
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